Клиническая иммунология рака молочной железы


DOI: https://dx.doi.org/10.18565/pharmateca.2022.7.29-36

Целуйко А.И., Семиглазов В.Ф., Кудайбергенова А.Г., Артемьева А.С., Палтуев Р.М., Донских Р.В., Песоцкий Р.С., Криворотко П.В.

Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова, Санкт-Петербург, Россия
Иммунология – бурно развивающаяся область в клинической онкологии. Комбинированная лекарственная терапия изучается при различных онкологических заболеваниях. За последние годы была разработана иммунотерапия, основанная на ингибировании контрольных точек моноклональными антителами, воздействующими на белок PD-1 и его лиганд PD-L1. Рак молочной железы в отличие от других опухолей относительно поздно стал рассматриваться в иммуноонкологии. В этом обзоре представлены результаты международных и собственных клинических исследований ингибиторов иммунных контрольных точек (ICI) в лечении различных биологических подтипов рака молочной железы. Также рассматриваются прогностическое и предиктивное значение уровня опухоль-инфильтрирующих лимфоцитов (TILs), в частности CD3, CD4, CD8, их корреляции с регуляторными генами (PD-1, PDL-1, FOX-P3).

Литература


1. Franzoi M.A., Romano E., Piccart M. Immunotherapy for early breast cancer: too soon, too superficial, or just right? Ann Oncology. 2021;32(3):323-336. Doi: 10.1016/j.annonc.2020.11.022.


2. Stanton S.E., Adams S., Disis M.L. Variation in the Incidence and Magnitude of TumorInfiltrating Lymphocytes in Breast Cancer Subtypes: ASystematic Review. JAMA Oncol. 2016;2(10):1354–60. Doi: 10.1001/jamaoncol.2016.1061.


3. Tseluiko A., Semiglazov V., Kudaibergenova A., et al. The role of tumor-infiltrating lymphocytes, prognostic and predictive signification in breast cancer. 17th St. Gallen International Breast Cancer Conference. The Breast 56S1(2021), P118, S65.


4. Loi S., Michiels S., Loibl S., et al. The journey of tumor-infiltrating lymphocytes as a biomarker in breast cancer: clinical utility in an era of checkpoint inhibition. Ann Oncol. 2021;32(10):1236–44. Doi: 10.1016/jannoc.2021.07.007.


5. Park J.H., Jonas S.F., Bataillon G., et al. Prognostic value of tumor-infiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapy. Ann Oncol. 2019;30(12):1941–49. Doi: 10.1093/annonc/mdz395.


6. De Jong V.M.T. Wang Y. Opdam M., et al. Prognostic value of tumour infiltrating lymphocytes in young triple negative breast cancer patients who did not receive adjuvant systemic treatment; by the PARADIGM study group. Ann Oncol. 2020;31:S303–39.


7. Urezkova M., Kudaybergenova A., Semiglazova T., et al. TILs in triple – positive breast cancer. 17th St Gallen breast cancer conference, 2021, Poster Abstract. The Breast 56S1(2021), P027, S17–90.


8. Loi S., Michiels S., Salgado R., et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol. 2014;25(8):1544–50. Doi: 10.1093/ annonc/mdu112.


9. Cimino-Mathews A., Thompson E., Taube J.M., et al. PD-L1 (B7-H1) expression and the immune tumor microenvironment in primary and metastatic breast carcinomas. Hum Pathol. 2016;47(1):52– 63. Doi: 10.1016/j.humpath.2015.09.003.


10. Liu F., Lang R., Zhao J., et al. CD8+ cytotoxic T cell and. FOXP3+ regulatory T cell infiltration in relation to breast cancer survival and molecular subtypes. Breast Cancer Res Treat. 2011;130(2):645–55. doi: 10.1007/s10549-011-1647-3.


11. I-SPY2 Trial Consortium, et al. Association of Event-Free and Distant Recurrence–Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer: Three-Year Follow-up Analysis for the I-SPY2 Adaptively Randomized Clinical Trial. JAMA Oncol. 2020;6(9):1355–62. Doi: 10.1001/ jamaoncol.2020.2535.


12. Terranova-Barberio M., Pawlowska N., Dhawan M., et al. Exhausted T cell signature predicts immunotherapy response in ER-positive breast cancer. Nat Commun. 2020;11(1):3584. Doi: 10.1038/s41467-020-17414-y.


13. Liu F., Li. Y., Ren M., et al. Peritumoral FOXP3+ regulatory T cell is sensitive to chemotherapy while intratumoral FOXP3+ regulatory T cell is prognostic predictor of breast cancer patients. Breast Cancer Res Treatment. 2012;135(2):459–67. Doi: 10.1007/s10549-012-2132-3.


14. Miyashita M., Sasano H., Tamaki K., et al. Prognostic significance of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in residual tumors and alterations in these parameters after neoadjuvant chemotherapy in triple-negative breast cancer: a retrospective multicenter study. Breast Cancer Res 2015;17(1):124. Doi: 10.1186/s13058-015-0632-x.


15. Denkert C., von Minckwitz G., Darb-Esfahani S., et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40–50. Doi: 10.1016/S1470-2045(17)30904-X.


16. Loi S., Drubay D., Adams S., et al: Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers. J Clin Oncol. 2019;37:559–69.


17. Schmid P., Adams S., Rugo H.S., et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108– 21. Doi: 10.1056/NEJMoa1809615.


18. Schmid P., Rugo H.S., Adams S., et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21(1):44–59. Doi: 10.1016/S1470-2045(19)30689-8.


19. Miles D., Gligorov J., André F., et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of firstline paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol. 2021;32(8):994–1004. Doi: 10.1016/j. annonc.2021.05.801.


20. Voorwerk l., Kok M. ‘IMpassionate conflicts’ in immunotherapy trials for metastatic triple-negative breast cancer. Ann Oncol. 2021;32(8):947–49. Doi: 10.1016/j.annonc.2021.06.019


21. Schmid P., Cortes J., Pusztai L., et al. Pembrolizumab for early triplenegative breast cancer. N Engl J Med. 2020;382(9):810–21. Doi: 10.1056/ NEJMoa1910549.


22. Cortes J., Cescon D.W., Rugo H.S., et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817–28. Doi: 10.1016/S0140-6736(20)32531-9.


23. Cain D.W., Cidlowski J.A. Immune regulation by glucocorticoids. Nat Rev Immunol. 2017;17(4):233–47. doi: 10.1038/nri.2017.1.


24. Petrelli F., Signorelli D., Ghidini M., et al. Association of steroids use with survival in patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis. Cancers (Basel). 2020;12(3):546. Doi: 10.3390/ cancers12030546.


25. Keenan T., Tolaney S. Role of immunotherapy in triple-negative breast cancer. J. Natl Compr Canc Netw. 2020;18(4):479–89. Doi: 10.6004/ jnccn.2020.7554.


26. Nanda R., Liu M.C., Yau C., et al. Effect of pembrolizumab plus neoadjuvant chemotherapy on pathologic complete response in women with earlystage breast cancer: an analysis of the ongoing phase 2 adaptively randomized I-SPY2 trial


27. Zitvogel L., Apetoh L., Ghiringhelli F., et al. Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2008;8(1):59–73. Doi: 10.1038/nri2216.


28. Loibl S., Schneeweiss A., Huober J.B., et al. Durvalumab improves long-term outcome in TNBC: results from the phase II randomized GeparNUEVO study investigating neodjuvant durvalumab in addition to an anthracycline/taxane based neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC). J Clin Oncol. 2021;39(suppl 15; abstr 506).


29. Liu M.C., Robinson P.A., Yau C., et al. Evaluation of a pembrolizumab-8 cycle neoadjuvant regimen without AC for high-risk early-stage HER2-negative breast cancer: results from the I-SPY 2 TRIAL. Presented at the 2019 San Antonio Breast Cancer Symposium; December 10–14, 2019; San Antonio, Texas. Abstract P3-09-02.


30. Schmid P., Cortes J., Pusztai L., et al. Pembrolizumab for early triplenegative breast cancer. N Engl J Med. 2020;382(9):810–21. Doi: 10.1056/ NEJMoa1910549.


31. Mittendorf E.A., Zhang H., Barrios C.H., et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020;396(10257):1090–100. Doi: 10.1016/ S0140-6736(20)31953-X.


32. Семиглазов В.Ф., Целуйко А.И., Балдуева И.А. и др. Иммунология и иммунотерапия в комплексном лечении злокачественных опухолей. Медицинский совет 2021;(4):248–257.


33. Gianni L, Huang C-S, Egle D, et al. Abstract GS3-04: Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple negative, early high-risk and locally advanced breast cancer. NeoTRIPaPDL1 Michelangelo randomized study. Cancer Res. 2020;80(4 suppl):GS3-04. Doi: 10.1158/1538-7445.sabcs19-gs3-04.


34. Zhang Y., Wang S., Yang B., et al. Adjuvant treatment for triple-negative breast cancer: a retrospective study of immunotherapy with autologous cytokine-induced killer cells in 294 patients. Cancer Biol Med. 2019;16(2):350–360. Doi: 10.20892/j.issn.2095-3941.2018.0378.


35. Loriot Y., Marabelle A., Guégan J.P., Danlos F.X. Plasma proteomics identifies Leukemia Inhibitory Factor (LIF) as a novel predictive biomarker of immune-checkpoint blockade resistance. Ann Oncol. 2021;32(11):1381–90. Doi: 10.1016/j. annonc.2021.08.1748.


36. Ali H.R., Provenzano E., Dawson S.-J., et al: Association between CD8+ T-cell infiltration and breast cancer survival in 12 439 patients. Ann Oncol. 2014;25(8):1536–43. Doi: 10.1093/ annonc/mdu191.


37. Tolaney S.M., Barroso-Sousa R., Keenan T., et al: Effect of Eribulin With or Without Pembrolizumab on Progression-Free Survival for Patients With Hormone Receptor–Positive, ERBB2-Negative Metastatic Breast Cancer: A Randomized Clinical Trial


Об авторах / Для корреспонденции


Автор для связи: Андрей Игоревич Целуйко, врач-онколог, НМИЦ онкологии им. Н.Н. Петрова, Санкт-Петербург, Россия; tselalex@rambler.ru 


ORCID:
А.И. Целуйко (A.I. Tseluiko), https://orcid.org/0000-0001-8384-5786
В.Ф. Семиглазов (V.F. Semiglazov), https://orcid.org/0000-0003-0077-9619
А.Г. Кудайбергенова (A.G. Kudaibergenova), https://orcid.org/0000-0002-2461-7721
А.С. Артемьева (A.S. Artemyeva), https://orcid.org/0000-0002-1935-7021
Р.М. Палтуев (R.M. Paltuev), https://orcid.org/0000-0002-0871-9453
Р.В. Донских (R.V. Donskikh), https://orcid.org/0000-0002-9391-5327
Р.С. Песоцкий (R.S. Pesotsky), https://orcid.org/0000-0002-2573-2211
П.В. Криворотко (P.V. Krivorotko), https://orcid.org/0000-0002-4898-9159


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